Affiliation:
1. The Children's Hospital at Westmead Clinical School University of Sydney Sydney Australia
2. Department of Biochemistry The Children's Hospital at Westmead Sydney Australia
3. Cancer Centre for Children The Children's Hospital at Westmead Sydney Australia
4. Sydney Pharmacy School Faculty of Medicine and Health University of Sydney Sydney Australia
5. Institute for Pharmaceutical and Medicinal Chemistry and Clinical Pharmacy University of Münster Sydney Germany
Abstract
N,N–dimethylacetamide is an excipient used in intravenous busulfan formulations, a drug used in hematopoietic stem cell transplantation conditioning. The aim of this study was to develop and validate a liquid chromatography‐tandem mass spectrometry method for simultaneous quantification of N,N‐dimethylacetamide, and its metabolite N‐monomethylacetamide in plasma from children receiving busulfan. A 4 μl aliquot of patient plasma was extracted using 196 μl 50% methanol solution and quantified against calibrators prepared in the extraction solvent given negligible matrix effects across three concentrations. 9[H2]‐N,N‐dimethylacetamide was used as an internal standard. Separation of N,N‐dimethylacetamide and N‐monomethylacetamide was achieved using a Kinetex EVO C18 stationary phase (100 mm × 2.1 mm × 2.6 μm) running an isocratic mobile phase of 30% methanol containing 0.1% formic acid at a flow of 0.2 ml/min over 3.0 min. The injection volume was 1 μl. Calibration curves for N,N‐dimethylacetamide and N‐monomethylacetamide were linear up to 1200 and 200 μg/L, respectively, with a lower limit of quantification 1 μg/L for both analytes. Calibrator accuracy and precision were within ± 10% of the test parameters across four concentration levels. Analytes were stable over 14 days at three different storage conditions. This method was successfully applied to measure N,N‐dimethylacetamide and N‐monomethylacetamide concentrations in a total of 1265 plasma samples from 77 children.
Subject
Filtration and Separation,Analytical Chemistry
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